Chidamide is a novel anticancer drug that is designed and synthesized by Chipscreen Co. Ltd. (Shenzhen, China) with a completely new chemical structure and worldwide intellectual property rights. The chemical name of chidamide is N-(2-amino-4-fluorophenyl)-4-(N-(3-pyridylacryloyl)aminomethyl)benzamide, with chemical structure of formula I:

As described in patent ZL 03139760.3 and U.S. Pat. No. 7,244,751, chidamide has the inhibition activity on histone deacetylases, and can be used in the treatment of differentiation and proliferation-related diseases, such as cancers and psoriasis, and particularly, it possesses excellent therapeutic efficacy on leucocythemia and solid tumors.
Although the preparation method of chidamide was disclosed in patent ZL 03139760.3 and U.S. Pat. No. 7,244,751, it was not indicated whether the product was a crystalline substance, nor whether there was polymorphism for the compound. In the patents mentioned above, the evaluation on the activities of the compound was not performed in solid state, and accordingly, there was no crystal characteristics-related description disclosed.
Crystal form is one of the key factors that affect the quality, therapeutic efficacy and formulation processing performance of the drug substance. Polymorphism refers to the phenomenon that one compound may form two or more molecular spatial arrangements by controlling the conditions and thus form different solid crystals. Polymorphism is a common phenomenon in the development of a drug substance, and is a key factor to affect the quality of a drug product. For different crystal forms of a compound, although they have the same chemical composition, they have different crystal structures, and result in differences in their external morphology, physicochemical properties and biological activities. Different crystal forms of a drug substance tend to be different in solubility, storage stability, hygroscopicity, density and bioavailability. The crystal form of a drug substance directly influences the quality of its pharmaceutical formulation and the absorbing behavior in the human body, and thus influences the therapeutic effect/side effect ratio in human body. Accordingly, it is of great significance to investigate the polymorphism of a drug substance and the preparation methods for different crystal forms.